The present invention relates to the use of dihydroergotamine and its salts for the local treatment of trophic disturbances which manifest themselves clinically in the form of stasis dermatoses, ulcers and tissue death. The invention also concerns drug dosage forms for local application which contain dihydroergotamine and/or its salts and are suitable for the treatment of trophic disturbances, as well as methods for the production thereof.
Trophic disturbances are nutrition-induced, and thus growth-induced, disturbances in the nutrition of the tissue or of organs, stasis dermatoses and ulcers of the veins of the lower leg (ulcus cruris venosum) being the most severe consequences of chronic venous insufficiency, caused by a constitutional, protonic weakening of the vein walls or the consequence of thrombotic diseases.
Another form of trophically-produced disturbances of the skin are decutibal ulcers, caused by regional disturbances in the circulation of immobilized bed-ridden patients.
From epidemiological studies it has been found that about 2% of the population of the industrial countries have ulcers in the region of their legs, about 90% thereof being caused by veins (Schmidle et al., Pharmakritic 8, 6, 1986, pages 21-24). It is clear from this that, in addition to the limited quality of life of the persons affected, considerable economic losses also result, due to stays in hospital and inability to work. Up to now there has been no clear standard medicinal treatment for ulcus cruris venosum, stasis dermatoses and decubital ulcers. Rather, these diseases are treated polypragmatically by symptomatic treatment, with results which in the final analysis are uncertain. In accordance with traditional medicine the treatment comprises cleaning the ulcer by mechanical, osmotic, or enzymatic methods, simultaneous antimicrobial or antiphlogistic treatment and the use of granulation-promoting and epithelizing agents (M. Morl, Fortschr. Med. 104, 1986, No. 21), generally with the application of pressure bandages in order to obtain venous flow physically, and lack of movement. The doubtful nature of these methods of treatment is described by Schmidli and Holzer in an article entitled "Lokale Behandlung von Hautulcera" [Local Treatment of Ulcers of the Skin] published in Pharmakritic 8, 6, 1986.
The use of dihydroergotamine and its salts in medicinal forms for peroral and parenteral application for promoting vasotonia in order to treat hypotonic orthostatic dysregulation (low blood pressure), attacks of migraine and chronic venous insufficiency as well as assure migraine prophylaxis is known.
The local application of dihydroergotamine for the treatment of trophic disturbances such as, for instance, stasis dermatosis, ulcus cruris venosum,and decubital ulcers has not been known up to the present time.
It has surprisingly been discovered that said diseases can be successfully treated if--contrary to the classical use of dihydroergotamine and its salts--they are applied locally. It was furthermore surprisingly found that wet and discharging open wounds in the case of ulcerations dry up after only a short time under the action even of liquid forms of administration. It is possible in such case to dispense completely with the use of antibiotics and cleansing agents for the control of the bacterial infections which customarily occur and make the treatment even more difficult. It was furthermore surprising that, after only a short period of time as compared with the customary time of treatment, vascularization from the depth of the ulcer could be observed as well as clearly visible granulation islands.
Furthermore, it was surprisingly found that the healing takes place both from the depth of the ulcer and from its edge by tissue growth, so that as a rule no cosmetic corrections are subsequently necessary. In this connection side effects which might be objectively expected, such as an increase in blood pressure, are absent.
Stasis dermatoses and post-thrombotic dermatitises which are characterized by scaling and frequently large-size medium-to-dark-brown spots surprisingly show a definite lightening of the color of the infected regions of the skin after only a short time following the use of dihydroergotamine in accordance with the invention. After treatment for several weeks, the color and elasticity of the skin have again adapted themselves to the normal surrounding area.